Extracellular Matrix Biology 1 Flashcards
What is ECM?
complex network of proteins and carbs between cells, includes fibrillar and non-fibrillar components
ECM functions
physical support
determines mechanical and physiochemical properties of tissue
influences growth, adhesion and differentiation status
essential for development, tissue function and organogenesis
What are the 3 components of connective issues?
collagens, multi adhesive glycoproteins, proteoglycans
Name human disorders that result from a gene mutation affecting matrix proteins and the protein affected
osteogenesis imperfect - type 1 collagen marfan's syndrome - fibrillar 1 alport's syndrome - type 4 collagen epidermolysis bullosa - laminin 5 congenital muscular dystrophy - laminin 2
Name a human disorder that result from a gene mutation affecting ECM catabolism and the protein affected
hurler’s Syndrome - L-alpha-iduronidase
What happens to organ when there is excessive ECM deposition? give disease examples
fibrosis of the organ
liver fibrosis - cirrhosis
kidney fibrosis - diabetic nephropathy
lung fibrosis - silicosis
Give an example of a disorder due to loss of ECM
osteoarthritis
Name the connective tissues and their properties
tendon/skin - tough and flexible
vitreous humour - soft and transparent
bone - hard and dense
cartilage - resilient and shock absorbing
What allows the different properties of connective tissues
ECM composition and components
What are collagens?
family of fibrous proteins
How can collagen resist tensile force?
successive layers at 90 degrees so resist force in all directions
What is the structure of collagen?
3 alpha chains in left handed triple helix and may have one or more different alpha chains
What is the alpha composition of type 1, 2 and 3 collagen?
type 1 - 2x alpha 1(I), 1x alpha 2(I)
type 2 - 3x alpha 1(II)
type 3 - 3x alpha 1(III)
What is every third amino acid on the triple helix of collagen and why?
glycine as small enough to occupy interior
What is required for lysine and proline hydroxylation? Why is it done?
Fe2+ and vitC for hydroxylases
contributes to interchain bond formation
How are lysine and hydroxy-lysine modified? Why?
covalent cross linkages after secretion to increase strength
What is the purpose of covalent cross links?
provide tensile strength and stability between or within the triple helix
What do fibril associated collagens do? give examples
type IX or XII
associate with fibrillar collagens and regulate organisation of collagen fibrils
what do network forming collagens do? give an example
type IV
assembles in a sheet like network in the basement membrane of all tissues with a varied molecular composition
What is the structure of elastic fibres?
core (protein elastin) and microfibrils rich in fibrillin
interwoven with collagen to limit stretching
What is the elastin structure?
hydrophobic segment and alpha helical segment
alpha helical rich in alanine and lysine
lysine side chains covalently linked
What is the function of basement membrane?
regulate tissue function, surround muscle/nerve/fat cells
Describe marfan’s syndrome
fibrillin-1 mutation reuslt in microfibril disruption
Describe diabetic nephropathy
ECM accumulation so basement membrane thickens so renal filtration restricted and renal failure
Describe alport syndrome
collagen type IV mutation so glomerulus basement membrane splits and laminated so decreased kidney function
What is the basement membrane?
flexible, thin mats of ECM underlying epithelial sheets and tubes
